转录因子KLF9通过PTEN依赖性调节有氧糖酵解克服乳腺癌的5-氟尿嘧啶耐药性

IF 1.9 4区医学 Q3 INFECTIOUS DISEASES

Journal of Chemotherapy Pub Date : 2024-11-03 DOI:10.1080/1120009X.2024.2421701

Liang Xu, Jing Sun, Junlan Guo, Shengnan Guo, Jiangli Li, Yijun Tang, Xiaohui Liu

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引用次数: 0

摘要

5-氟尿嘧啶（5-FU）耐药性的出现是乳腺癌化疗的一个主要问题。本文深入研究了PTEN在乳腺癌对5-FU耐药性中的作用，并探讨了其背后的分子通路。在生物信息学数据库中检测了 PTEN 的表达，并确定了上游转录因子 (TF)。测量了 PTEN mRNA 和蛋白水平、有氧糖酵解蛋白、乳酸生成、葡萄糖消耗和细胞活力。确认了结合相互作用，并对细胞增殖进行了评估。在乳腺癌细胞中，PTEN 的表达被下调。PTEN 的过表达通过抑制有氧糖酵解而抵消了 5-FU 抗性。KLF9 作为 PTEN 上游的 TF，可提高 PTEN 的水平。总之，TF KLF9通过上调PTEN的表达来抑制乳腺癌细胞的有氧糖酵解水平，从而降低它们对5-FU的耐药性。这一机制的发现为乳腺癌的治疗提供了新的理论依据。

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Transcriptional factor KLF9 overcomes 5-fluorouracil resistance in breast cancer via PTEN-dependent regulation of aerobic glycolysis.

The emergence of resistance to 5-Fluorouracil (5-FU) is a staple in breast cancer chemotherapy. This paper delves into the role of PTEN in breast cancer resistance to 5-FU and examines the underlying molecular pathways. PTEN expression was detected in bioinformatics databases and upstream transcription factors (TFs) were identified. PTEN mRNA and protein levels, aerobic glycolysis proteins, lactate production, glucose consumption, and cell viability were measured. Binding interactions were confirmed, and cell proliferation assessed. In breast cancer cells, PTEN expression was downregulated. PTEN overexpression counteracted 5-FU resistance through the suppression of aerobic glycolysis. KLF9, as a TF upstream of PTEN, enhanced the levels of PTEN. In conclusion, the TF KLF9 inhibits the aerobic glycolysis level of breast cancer cells by up-regulating PTEN expression, thereby reducing their resistance to 5-FU. The discovery of this mechanism provides a new theoretical basis for the treatment of breast cancer.

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来源期刊

Journal of Chemotherapy 医学-药学

CiteScore

3.70

自引率

0.00%

发文量

144

审稿时长

6-12 weeks

期刊介绍： The Journal of Chemotherapy is an international multidisciplinary journal committed to the rapid publication of high quality, peer-reviewed, original research on all aspects of antimicrobial and antitumor chemotherapy. The Journal publishes original experimental and clinical research articles, state-of-the-art reviews, brief communications and letters on all aspects of chemotherapy, providing coverage of the pathogenesis, diagnosis, treatment, and control of infection, as well as the use of anticancer and immunomodulating drugs. Specific areas of focus include, but are not limited to: · Antibacterial, antiviral, antifungal, antiparasitic, and antiprotozoal agents; · Anticancer classical and targeted chemotherapeutic agents, biological agents, hormonal drugs, immunomodulatory drugs, cell therapy and gene therapy; · Pharmacokinetic and pharmacodynamic properties of antimicrobial and anticancer agents; · The efficacy, safety and toxicology profiles of antimicrobial and anticancer drugs; · Drug interactions in single or combined applications; · Drug resistance to antimicrobial and anticancer drugs; · Research and development of novel antimicrobial and anticancer drugs, including preclinical, translational and clinical research; · Biomarkers of sensitivity and/or resistance for antimicrobial and anticancer drugs; · Pharmacogenetics and pharmacogenomics; · Precision medicine in infectious disease therapy and in cancer therapy; · Pharmacoeconomics of antimicrobial and anticancer therapies and the implications to patients, health services, and the pharmaceutical industry.